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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Sept 18, 2014

A mother rhesus macaque and her infant at the California National
Primate Research Center at University of California Davis.

Image Credit: Kathy West, California National Primate Research Center

 






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Infant's diet creates unique immune systems

Infant rhesus macaque monkeys receiving different diets early in life developed distinctly different immune systems that persisted for months after weaning.

While the researchers expected different diets would promote different intestinal bacteria (microbiota), they were surprised how dramatically these microbes shaped immune system development.

The study was conducted by researchers from UC Davis, the California National Primate Research Center (CNPRC) at UC Davis and UC San Francisco, and appears online in Science Translational Medicine.


Specifically, breast-fed macaques had more "memory" T cells and T helper 17 (TH17) cells, which are known to fight Salmonella and other pathogens.

These differences persisted for months after the macaques had been weaned and placed on identical diets, indicating that variations in early diet have long-lasting effects.


"We saw two different immune systems develop: one in animals fed mother's milk and another in those fed formula. But what's most startling is the durability of these differences. Infant microbes could leave a long-lasting imprint on immune function," said Dennis Hartigan-O'Connor, a CNPRC scientist in the Infectious Diseases Unit and Reproductive Sciences and Regenerative Medicine Unit, and an assistant professor in the Department of Medical Microbiology and Immunology at UC Davis.

Previous research has revealed the relationship between breast milk, microbiota and the developing immune system. Sugars in breast milk, for example, help grow specific bacteria that support specific immune cells. This new study reveals how separate pieces of the immune system link together and might influence an immune response to infection or vaccination.


Macaques are born with virtually no TH17 cells, which then develop during their first 18 months of life. Hartigan-O'Connor and others observed some macaques develop large TH17 cell populations, while others have few — which could profoundly affect an animals' ability to fight infection, particularly the simian strain of HIV known as SIV.

To understand this variation, investigators followed six breast-fed and six bottle-fed rhesus macaques from age five months to 12 months. At six months, they found significant differences in the two groups' microbiota.


Specifically, breast-fed macaques had larger numbers of Prevotella and Ruminococcus bacteria, while bottle-fed macaques had an abundance of Clostridium. Overall, the microbiota in breast-fed macaques was more diverse than in the bottle-fed group.

The big surprise came when examining their immune systems. By 12 months, the two groups showed significant contrasts, with the differences centered on T cell development. The breast-fed group had a much larger percentage of experienced memory T cells, which are better equipped to secrete immune defense chemicals (cytokines) including TH17 and interferon-producing cells.


"This is the first time researchers have shown that immunologic characteristics may be imprinted in the first months of life. Our study suggests that gut microbiota present in early life may leave a durable imprint on the shape and capacity of the immune system, programming the system if you will."  

Amir Ardeshir PhD, the study's first author.


Further investigation may have identified chemicals that drive these differences. For example, arachidonic acid, which stimulates the production of TH17 cells and is found in macaque breast milk, was tightly linked to TH17 cell development. Previous studies have suggested it can influence T cell development. The researchers caution that these chemicals must be tested in larger studies to understand their effects.

While this research provides a fascinating window into immune cell development in macaques, Hartigan-O'Connor cautions it doesn't prove the same mechanisms exist in people. The lab is planning similar studies in humans to test that hypothesis. In addition, this study does not prove a link between breastfeeding and better health.

Hartigan-O'Connor: "There's a developmental shape to the immune system that we don't often consider. It's dramatic how that came out in this study. There's a lot of variability in how both people and monkeys handle infections, in their tendency to develop autoimmune disease, and in how they respond to vaccines. This work is a good first step towards explaining those differences."

Abstract
Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases.

Other authors include: Nicole Narayan, Gema Mendez-Lagares, Ding Lu, and Koen K. A. Van Rompay, Marcus Rauch, Susan V. Lynch and Yong Huang at UC San Francisco.

This research was supported by grants from the National Institute of Allergy and Infectious Diseases (K23AI081540), the Bill and Melinda Gates Foundation under a Grand Challenges Exploration award (#52094) and by Office of the Director of NIH (P51-OD011107).


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